Acceptability, feasibility and impact of routine
screening to detect undiagnosed HIV infection in 17-24-month-old
children in the western sub-district of Cape Town.

Abstract:

Objectives. To explore the acceptability and feasibility of routine
HIV screening in children at primary healthcare clinics and ascertain
the prevalence of previously undiagnosed HIV infection in
17-24-month-old children accessing curative and routine services.

Methods. A survey was conducted in 4 primary health clinics in the
western sub-district of Cape Town. Rapid HIV screening of 17-24-month
old children was performed for consenting caregiver-child pairs. Data on
demographics, child health and antenatal history were collected using
questionnaires.

Results. During recruitment, 358 children (72%) were tested for HIV
infection. Most of the children (95.8%) were accompanied by a parent.
The prevalence of reported HIV exposure among children was 21%
(107/499). Of these, 3 had previously confirmed HIV infection; 1 was
reportedly confirmed by a 6-week HIV test, and the other 2 probably
contracted the virus via late postpartum transmission. The overall
transmission rate was 3.5% (3/86) and the confirmed proportion of
HIV-infected children was 0.8% (3/361). No previously unknown HIV
infection was detected.

Conclusions. Programmes to prevent mother-to-child transmission are
effective, but at-risk infants who test negative at 6 weeks should be
monitored for subsequent seroconversion. Parents of HIV-exposed infants
are more likely to permit (re)testing of their infants than those whose
offspring are not at risk. Routine HIV testing of children is feasible
and acceptable at primary level, but may require additional resources to
achieve universal coverage. Routine screening at an earlier age may
detect previously undiagnosed HIV infection.

Mother-to-child transmission (MTCT) contributes significantly to
the incidence of HIV in sub-Saharan Africa and the rising number of
children contracting HIV. In 2007 it was estimated that about 300 000 of
South Africa's 5.5 million HIV-infected persons were children; (1)
this rose to 330 000 of 5.6 million in 2009. (2)

Prevention of mother-to-child transmission (PMTCT) strategies
include the South African PMTCT programme that incorporates
interventions antepartum, during labour and delivery, and postpartum.
(3,4) Despite comprehensive guidelines, service and patient-related
challenges compromise the effectiveness of the PMTCT programme, leading
to the identification of children with previously undiagnosed HIV
infection at public health facilities. These challenges include
suboptimal PMTCT programme coverage, late presentation for the first
antenatal visit, maternal seroconversion after the first visit with
insufficient repeat testing in late pregnancy, and suboptimal postpartum
follow-up. (5)

The coverage of antiretroviral (ARV) prophylaxis and antiretroviral
therapy (ART) initiation remains inadequate. The coverage of
short-course zidovudine is poorly documented. The national coverage for
single-dose nevirapine between 2007 and 2008 was 76%, (6) and a study in
Cape Town reported that treatment was initiated in only 51% of pregnant
women eligible for ART. (7)

An opportunity for prevention is missed when undiagnosed
HIV-positive pregnant women are not identified by services. Booking
should optimally occur at 14 weeks' gestation and HIV status tested
at the initial visit. Patients who refuse testing should be counselled
to test at subsequent visits. Repeat HIV testing at 32-34 weeks for
women who test negative in early pregnancy is national PMTCT policy. (4)
However, this is often poorly implemented. In Botswana, a study
attributed 43% of all MTCT of HIV to seroconversion in late pregnancy
and postpartum, (8) highlighting the increased risk of unknown MTCT
without re-testing.

Low coverage of postpartum follow-up services creates more
opportunities for MTCT. National and Western Cape province PMTCT
guidelines include repeat testing for HIV-exposed children who tested
negative at 6 weeks. (3,4,9,10) In the case of breastfed infants, this
is performed 6 weeks after breast-feeding is ceased. National guidelines
also provide for re-testing of all HIV-exposed children at 18 months of
age, but Cape Town City Health data show that few repeat tests are done.
(5) Furthermore, the risk of MTCT increases if mothers contract HIV
postpartum; therefore, health services may not identify children with
HIV in good time.

We explored the acceptability and feasibility of routine HIV
screening in children at primary healthcare clinics to ascertain the
proportion of previously undiagnosed HIV-positive children aged 17-24
months accessing curative and routine child healthcare services.

Methods

This was an exploratory, facility-based cross-sectional study in
the western sub-district of Cape Town. Primary healthcare facilities
offering immunisation services (Du Noon, Albow Gardens, Vanguard and
Langa) were non-randomly selected based on clinic size.

Fieldworkers recruited all patients aged 17-24 months as they
arrived to access health services. Paediatric HIV clinics were excluded
from the study, but patients on HIV registers seeking other curative or
routine health services were eligible. No sample size calculations were
performed due to the exploratory nature of the study. The target
recruitment number of 500 patients, realised between September 2010 and
February 2011, was based on Cape Town City Health statistics for the
number of children accessing routine 18-month immunisation services over
3 months.

Healthcare providers (HCPs) provided the required consultation to
children and their caregivers. To facilitate routine screening, HCPs
implemented a streamlined approach to provider-initiated HIV counselling
and testing (PICT). (11) PICT was introduced prior to commencement of
the study and all healthcare workers were trained accordingly. The
Abbott Determine HIV antibody test was used to detect HIV infection.
Known HIV-positive children were not screened. Caregivers could decline
the testing of their children even in the case of prior consent.

Data were captured into a secure Microsoft Access database,
validated and audited to ensure quality. Data analysis was performed
using STATA Data Analysis and Statistical Software (release 11).

This was a non-anonymous study at primary healthcare facilities.
Ethical approval was granted by the Health Sciences Research Ethics
Committee at the University of Cape Town. Approval was also obtained
from Cape Town City Health and the Western Cape Department of Health.

Results

During recruitment, 567 caregiver-child pairs were identified as
potential participants (Fig. 1); 91% of caregivers were able to give
legal consent but 3% declined, making the final number of participant
pairs 499. A parent accompanied 95.8% (478/499) of children, including
97.2% (104/107) of HIV-exposed children and 95.4% (374/392) of
non-exposed children.

Ninety-nine per cent of pregnancies had been booked for delivery in
an obstetric unit or hospital. The reported HIV prevalence of mothers
was 21% (107/499). All except for 3 HIV infections were detected at
early booking; these women tested negative at first booking, testing
positive in late pregnancy, shortly post-partum and at recruitment,
respectively. To their knowledge, 87% of all HIV-infected mothers had
been on the PMTCT programme.

During recruitment, 72% of infants (358/499) were tested for HIV.
The highest uptake of infant testing was in known HIV-positive mothers
(83/107; 77.6%), followed by known HIV-negative mothers (267/368; 72.6%)
(Fig. 1). The lowest uptake was in mothers of unknown or undisclosed
status (8/24; 33.3%), which differed from the expected trend for random
refusal to test (Table 1). An overall chi-squared test confirmed a
significant association between the uptake of HIV testing and maternal
HIV status ([chi square](2)=21.07, p<0.001). There was no significant
difference in testing between HIV-positive and HIV-negative participants
who disclosed maternal HIV status ([chi square]=2.66, p=0.103). However,
a significantly lower uptake of testing was found by those participants
whose HIV status was unknown or undisclosed compared with known
HIV-infected mothers ([chi square]=21.40, p<0.001) and those known to
be uninfected ([chi square]=16.55, p<0.001).

No previously unknown HIV infection was detected. However, 87.9%
(94/107) of known HIV-positive mothers (18.8% of total cohort) reported
that their children were screened with HIV polymerase chain reaction
(PCR) tests at 6 weeks. Of these, 1 child tested positive. In addition,
79 children had been tested for HIV in infancy (some were exposed to HIV
but tested negative at 6 weeks). Two tested HIV-positive and were
diagnosed with HIV infection in the 2 months preceding recruitment,
because of intercurrent illness. One of these tested negative at 6
weeks. The other accessed PMTCT services in a neighbouring country, but
it is uncertain whether the child had a 6-week HIV PCR test. The 6-week
HIV transmission rate in this sample was 1.1% (1/94), the confirmed
overall transmission rate was 3.5% (3/86), and the proportion of
HIV-infected children (among those with confirmed HIV status) between
17-24 months of age was 0.8% (3/361). The HIV status of 28% (138) of the
children remained unknown as they were not tested.

Ninety-two per cent (98/107) of HIV-exposed infants were reportedly
never breastfed. The remaining 9 (8%) were exclusively breastfed (EBF)
in the first 6 months. After this time, breast-feeding was ceased in
favour of replacement feeding (formula and/or solid food) in 7 of the
infants and 2 mothers reported mixed feeding. In the latter, the status
of 1 mother was previously unknown; she tested HIV-positive on the day
of recruitment, but her child tested negative.

The 2 children diagnosed with HIV in the 2 months preceding
recruitment were EBF in the first 6 months and replacement-fed
thereafter. One was reported to be HIV-negative at 6 weeks (PCR test),
therefore infection may have been transmitted via breastfeeding.

Discussion

The percentage of HIV-exposed infants (21%) was in keeping with the
antenatal HIV prevalence reflected by a survey in 2009. (12) Overall,
this was 18.2% (95% CI 17.0-19.3) and 17.0% (95% CI 14.1-20.0) in the
Metro and western sub-districts, respectively. The higher result in our
study may have been attributed to the smaller sample size, or the higher
proportion of at-risk infants returning to follow-up clinics compared
with those not at risk. It is more likely that our findings reflect the
high prevalence of HIV in the low socioeconomic profile areas of Du
Noon, Langa and Bonteheuwel. A comparable sub-district of Klipfontein
has an HIV exposure rate of 24% (CI 21.0-27.1).

We found a low burden of HIV infection (0.8%) in 17-24-monthold
children attending clinics for curative and routine visits. To our
knowledge, this is the first published study of HIV burden in this age
group in South Africa. This prevalence is lower than that estimated in
the 2008 Human Science Research Council survey (1.1% among children aged
2-14 years in the Western Cape). (13) While this could attest to
effective PMTCT programme coverage, it is unclear whether the overall
population is represented in these findings. The reported 6-week
transmission rate of 1.1% was lower than the 2008/2009 provincial
estimate of 4.5%. (14) This could be attributed to differences in the
study sites or because of participant selection bias.

Moreover, this raises questions about the patterns of access to
health services among HIV-infected children. Up to 40% of HIV-exposed
children may be lost to follow-up services by 18 months of age. (15) The
median survival time of untreated perinatally infected children is 1.1
years. (16) HIV-related mortality rates are very high in the first year
of life, especially when ART is not initiated early. (17) Children in
this age group with unknown HIV infection may present with advanced
disease at secondary and tertiary healthcare facilities before 18 months
of age. One of the 2 HIV-positive children diagnosed in the 2 months
preceding recruitment in this study was diagnosed at a secondary level
institution. Furthermore, HIV-infected children who survive hospital
admission may be followed up and immunised in hospital-based services
before referral to primary level services. Three of the 4 study clinics
had a designated HIV clinic (excluded from recruitment) which may have
provided routine health services including immunisations. Therefore, the
low burden of HIV in this study does not account for HIV-infected
children being sick, accessing health services elsewhere, or dying
before their 18 month immunisation visit.

The overall transmission rate for participants was 3.5% (3 cases).
This included a case of perinatal transmission (6-week HIV PCR test
proved positive), and at least 1 case of postpartum transmission
probably from breast-feeding (reported negative 6-week HIV PCR test).
The age of the participant in the third case indicated that HIV
contraction was also possibly via breast-feeding.

In this study, routine HIV testing of children was feasible and
acceptable. Despite preconceptions of high rates of caregiver rotation
at child health services, a high proportion of children accessed health
services with a biological parent. This argues against routine HIV
testing not being feasible due to legal issues when children are not
accompanied by a guardian. The high rates of consent in this study
reflect the acceptability of an HIV testing service to clients, as
demonstrated in KwaZulu-Natal and Limpopo provinces. (18) Our research
also suggests that mothers are not opposed to PICT, which is part of the
HIV component of the South African Integrated Management of Childhood
Illness guidelines.

Managers at the research sites commented that the testing of
children led some mothers to confirm their own status. The
implementation of a more efficient approach to testing is valuable in
integrating and streamlining a service with a sizeable impact on
maternal and child health. (11)

Despite consenting to the study, only 72% of participants were
tested for HIV. Reasons for declining testing were not determined.
Researchers reported that some mothers retracted consent to avoid the
trauma of additional procedures such as HIV testing on the same day as
immunisations. This may indicate a need for additional resources to
allow universal coverage.

This does not account for the discrepancy in consent to testing
according to maternal HIV status. Known HIV-positive mothers were more
likely to consent to the testing of their children (78%) than uninfected
mothers (73%). The low rate of consent by mothers of unknown or
undisclosed HIV status (33.3%) may indicate that known HIV-positive
mothers perceive more benefit in re-testing their children. This could
reflect a lack of knowledge of the possibility of late pregnancy and
postnatal maternal acquisition of HIV. Mothers who have never been
tested or refuse to acknowledge their results may be in denial about
their HIV status or risk, thereby denying their children HIV screening
and possible early detection.

Our results question whether routine screening of HIV in children
should occur at all, and if so, whether at 18 months or at earlier
routine healthcare visits. Two of the 3 confirmed cases of HIV were
detected within 2 months of the study and could have been detected by
earlier screening. Many children still present with undiagnosed HIV in
the first year of life. Earlier diagnosis would lower HIV morbidity and
mortality, (17) especially in perinatal MTCT. (16)

It is important to consider the decline in access to services after
the first year of life. (15,19) Routine immunisation coverage in the
Western Cape drops to just over one half by 18 months of age. (19)
Mothers do not wish to have invasive procedures (immunisations) and
investigations (HIV test) performed on the same day; therefore, it would
be preferable to link HIV testing to other routine health visits. Many
mothers, however, only bring their children for immunisation visits.
Furthermore, the Department of Health has called for the cessation of
the free distribution of milk formula at health services, instead
promoting EBF for the first 6 months of life--regardless of maternal
HIV-status--together with ART provision to HIV-infected mothers and
their infants. (20) It may be advisable to recommend routine HIV tests
after 7 months of age (e.g. at 9 months), but this does not take into
account HIV-positive mothers who continue breast-feeding after 9 months
of age whose children may require yet another follow-up test.

Since the additional cases detected arose in the HIV-exposed group,
it is important to question whether there is any value in screening
children of HIV-negative women. There may be more benefit to screening
HIV-exposed children and previously HIV-negative women to detect
seroconversion and test the infants accordingly.

The generalisability of the findings is hindered by the
study's limitations. As an exploratory study, the sample size and
study area were both small. These are unlikely factors in other
programmes in the province and country. The probability of participant
selection bias should be mentioned, including an apparent 'healthy
child' effect at primary healthcare level. Furthermore, given the
high rates of institutional booking of pregnancies and deliveries in
this study, the caregiver-child pairs may have been more likely to
access postnatal public health services than those who do not access
antenatal care or deliver at health facilities.

Despite these limitations, lessons can be learned in terms of best
practice, opportunities to be seized, and what these mean for the PMTCT
programme and child health. The low burden of HIV demonstrates an
effective PMTCT programme, but testing protocols must identify HIV
infection not detected at 6 weeks, especially in breastfed children.
Routine PICT is an acceptable and feasible service. The effect of
routine HIV testing at 7-9 months of age should be assessed.

Funding acknowledgement. This research was funded by the US
President's Emergency Plan For AIDS Relief (PEPFAR) through the
United States Agency for International Development (USAID) under the
terms of Award No. 674-A-00-08-00009-00 to Anova Health Institute, as
well as the City of Cape Town.

USAID disclaimer. The opinions expressed herein are those of the
authors and do not necessarily reflect the views of USAID or PEPFAR.

(7.) Stinson K, Myer L, Boulle A. An evaluation of the approaches
to the initiation of antiretroviral therapy during pregnancy among
HIV-infected women in Cape Town. Cape Town: University of Cape Town,
2008.

(9.) Provincial Government of the Western Cape--Department of
Health. Policy and guidelines for the prevention of mother-to-child
transmission of HIV. Cape Town: Provincial Government of the Western
Cape, 2009.

(10.) Provincial Government of the Western Cape--Department of
Health. Circular No: H20/2011--Re: PMTCT protocol--Implementation of
revised PMTCT guidelines.

(12.) HIV and Syphilis Prevalence in the Western Cape: Results of
the 2009 HIV and syphilis antenatal provincial and sub-district surveys.
Cape Town: Provincial Government Western Cape, Department of Health,
2009.